D-glucose is used as a feedstock in the Reichstein synthesis of L-ascorbic acid (a form of vitamin C; ˜105 tons produced annually worldwide) via L-sorbose intermediates. The conversion of D-glucose to L-sorbose currently requires the sequential hydrogenation of D-glucose to D-sorbitol over a nickel-based catalyst and selective oxidation of C2-OH groups in D-sorbitol to L-sorbose using microbiological enzymes. The production of sorbose, among a mixture of several aldohexose and ketohexose isomers, has been observed during reactions of glucose in alkaline media via 3,4-enediol intermediates, and via retro-aldol condensation to glyceraldehyde, isomerization to dihydroxyacetone, and realdolization of these triose intermediates. Heterogeneous base resins (Amberlite XE-48, Amberlite IRA-400) also convert D-(+)-glucose to a mixture of D-(+)-sorbose (˜68%) and L-(−)-sorbose (˜32%), among several other hexose products, via 3,4-enediol intermediates.
Glucose isomerization and epimerization reactions catalyzed by bases are known to proceed via abstraction of α-carbonyl protons to form 1,2-enediol intermediates, which undergo proton-transfer mediated rearrangements to form fructose and mannose (Lobry de Bruyn-Alberda van Ekenstein rearrangements; LdB-AvE). Double-bond isomerization of 1,2-enediols leads to a mixture of 2,3- and 3,4-enediol intermediates that are precursors to psicose, tagatose and sorbose ketohexoses (the C-3, C-4 and C-5 epimers of fructose, respectively) and other aldohexoses. As a result, selectivities to fructose, the preferred product of glucose conversion in alkaline media, decrease with increasing glucose conversion because of sequential 1,2-enediol rearrangements and because monosaccharides undergo retro-aldol condensation and other degradation pathways.
In contrast to base catalysts that initiate glucose isomerization via α-carbonyl abstraction, Lewis acids coordinate with and polarize oxygen atoms (O1) at glucose aldehyde carbons (C1) to enable nucleophilic addition preferentially at electron-deficient C-1 centers over other carbon atoms along the sugar backbone. (FIG. 1A) The ability of a single Lewis acid center to coordinate with glucose via a second oxygen atom located in another hydroxyl group along the sugar backbone, in turn, facilitates intramolecular skeletal rearrangements via migration of nucleophilic moieties to glucose C1 centers. Infrared (IR) and solid-state 13C nuclear magnetic resonance (NMR) studies, together with quantum chemical calculations, have shown that Lewis acidic framework Sn centers isolated within zeolite beta (Sn-Beta) mediate glucose ring-opening and coordination with glucose O1 and O2 atoms. In turn, glucose-fructose isomerization occurs via subsequent intramolecular hydride shift from the C2 to C1 carbon atoms on open glucose chains. This isomerization mechanism is analogous to that mediated by two divalent Lewis acid metal centers (e.g., Mg2+ or Mn2+) that are spatially positioned within hydrophobic pockets of metalloenzymes (e.g., D-xylose isomerase) to facilitate glucose binding via O1 and O2 atoms prior to glucose-fructose isomerization.
Sn-Beta can also mediate glucose-mannose epimerization in methanol solvent, and in water in the presence of borate salts, via a Lewis-acid intramolecular carbon rearrangement known as the Bilik reaction. In the glucose-mannose epimerization mechanism, C3 carbon centers bound to C2 atoms behave as nucleophiles and migrate (along with the rest of the covalently bound sugar backbone) to electrophilic C1 centers (FIG. 1B). The mechanisms for framework Sn-mediated glucose-mannose epimerization and glucose-fructose isomerization are similar because they first require bidentate glucose coordination to metal centers via O1 and O2 atoms; they differ, in part, because C3 centers or hydridic species bound to glucose C2 centers respectively act as the nucleophiles that attack electron-deficient C1 centers (FIG. 1B). These intramolecular hydride and carbon shifts occur within glucose only with Lewis acidic framework Sn-Beta and not with base sites on extra framework SnO2 domains, reflecting the requirement of Lewis acid centers to mediate the redistribution of oxidation states between carbon atoms in organic substrates at transition states for intramolecular or intermolecular Meerwein-Ponndorf-Verley aldehyde and ketone reduction and Oppenauer alcohol oxidation (MPVO) reactions.